CB1 cannabinoid receptor agonist prevents NGF-induced sensitization of TRPV1 in sensory neurons.
CB1 cannabinoid receptor agonist prevents NGF-induced sensitization of TRPV1 in sensory neurons.
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DOI：
10.1016/j.neulet.2013.06.066
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发表时间：
2013-09-13
影响因子：
2.5
通讯作者：
Bjorling D
中科院分区：
文献类型：
--
作者：
McDowell TS;Wang ZY;Singh R;Bjorling D
瞬时受体电位VI型通道(TRPV1)和神经生长因子(NGF)是炎症性疼痛的重要介质。炎症过程中释放的NGF使外周伤害性感受器传入神经末梢的TRPV1敏化，增加痛感。大麻素通过激活CB1G蛋白偶联受体，在各种疼痛模型中产生镇痛作用，尽管确切的机制尚不清楚。我们验证了大麻类化合物激活CB1受体可减弱NGF诱导的TRPV1敏化的假设。以辣椒素(100 NM)为激动剂，采用全细胞膜片钳技术，在急性分离的初级感觉神经元上记录了TRPV1介导的电流。在第一次应用辣椒素后，测量基线电流，细胞暴露于NGF(100 ng/mL)中，5分钟后重复应用辣椒素。NGF使TRPV1致敏的细胞占31.0%(13/42)，辣椒素诱发电流的平均(±SE)较基线电流增加262±47%。当在NGF前给予大麻素激动剂ACEA(花生-2‘-氯乙胺；10 nM)时，只有10.8%的细胞(4/37)被致敏(p<；0.05)。这一比率和致敏程度(基线的198±63%)与未经NGF处理的细胞(25个细胞中致敏的3个细胞(12.0%)，基线的253±70%)没有不同。预先给予CB1拮抗剂AM-251(100 NM)可阻断ACEA对NGF诱导的致敏作用。这些结果支持这样一种假设，即大麻素通过CB1受体发挥作用，可能部分通过阻止NGF在传入伤害性神经末梢对TRPV1的敏化而产生镇痛作用。
The transient receptor potential vanilloid type 1 channel (TRPV1) and nerve growth factor (NGF) are important mediators of inflammatory pain. NGF released during inflammation sensitizes TRPV1 in afferent nerve endings of peripheral nociceptors, increasing pain sensation. Cannabinoids, by activating CB1 G protein-coupled receptors, produce analgesia in a variety of pain models, though the exact mechanisms are not known. We tested the hypothesis that activation of the CB1 receptor by cannabinoids attenuates NGF-induced TRPV1 sensitization. TRPV1-mediated currents were measured in acutely isolated primary sensory neurons with the whole-cell patch clamp technique using capsaicin (100 nM) as the agonist. After the first capsaicin application, during which the baseline current was measured, cells were exposed to NGF (100 ng/mL), and the capsaicin application was repeated after 5 minutes. NGF sensitized TRPV1 in 31.0 % of cells (13 of 42), with a mean (± SE) increase in the capsaicin-induced current of 262 ± 47 % over the baseline current. When the cannabinoid agonist ACEA (arachidonoyl-2’-chloroethylamide; 10 nM) was given before NGF, only 10.8 % of cells (4 of 37) were sensitized (p < 0.05). Neither this rate, nor the magnitude of the sensitization (198 ± 63 % of baseline) were different from that seen in cells not treated with NGF (3 of 25 cells sensitized (12.0 %), 253 ± 70 % of baseline). Pretreatment with the CB1 antagonist AM-251 (100 nM) prevented the effect of ACEA on NGF-induced sensitization. These results support the hypothesis that cannabinoids, acting through CB1 receptors, may produce analgesia in part by preventing NGF-induced sensitization of TRPV1 in afferent nociceptor nerve endings.
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DOI：
10.1073/pnas.0603861103
发表时间：
2006-07-25
影响因子：
11.1
作者：
Patwardhan, Amol M.;Jeske, Nathaniel A.;Hargreaves, Kenneth M.
通讯作者：
Hargreaves, Kenneth M.
影响因子：
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作者：
Mitrirattanakul, Somsak;Ramakul, Navapoln;Spigelman, Igor
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Spigelman, Igor
影响因子：
2.1
作者：
Priestley, JV;Michael, GJ;Willmott, N
通讯作者：
Willmott, N
影响因子：
2.5
作者：
Potenzieri, Carl;Brink, Thaddeus S.;Simone, Donald A.
通讯作者：
Simone, Donald A.
影响因子：
3.3
作者：
Ahluwalia, J;Urban, L;Nagy, I
通讯作者：
Nagy, I